Matrix Metalloproteinase-9 Gene Polymorphisms in South-West Iranian Multiple Sclerosis (MS) Patients

Abstract

Background: Matrix metalloproteinases (MMPs) play important role in Multiple Sclerosis (MS), an autoimmune and neuro-inflammatory disease. It has been demonstrated that two important polymorphisms, the –1562 C/T and microsatellite (CA)_n near the –90 position in the promoter region of MMP-9 gene are associated with increased MMP-9 expression, through influencing transcriptional process in MS, also some autoimmune diseases as well as cancers. In this study, the possible association of these gene polymorphisms with MS susceptibility, severity as well as age of onset in samples from south-west of Iran were examined. Methods: Polymorphisms for two regions, –1562 C/T (rs3918242) and –90 (CA)_n repeat was analyzed in 170 south-west Iranian patients with MS and 200 healthy controls. Results: Results suggested that a genetic polymorphism of the MMP-9 promoter region may influence the susceptibility to MS. Significant increase frequencies of the –1562 T and long (CA)_n alleles were found in patients with MS compared to controls. Carriers of two polymorphisms were younger age at disease onset. The disability status of patients, moreover, has been consistently increased by the association of T variants. Conclusion: This study suggests that genotypes and alleles of MMP-9 –1562 C/T gene as well as (CA)_n polymorphisms are associated with higher MS susceptibility due to increased MMP-9 protein levels. This finding, therefore, supports the hypothesis of a significant role of this gene in the disease.